Adding a Coefficient for Race to the 4Kscore Improves Calibration for Black Men.

PURPOSE: Black men face a higher incidence of high-risk prostate cancer (PCa) compared with non-Black men. While the 4Kscore is a widely utilized commercial test for PCa risk assessment, it does not currently account for racial differences. The aim of this study is to describe and validate a prespecified race coefficient for the 4Kscore with the goal of improving the accuracy of this test for Black men. MATERIALS AND METHODS: Using data from 85 Black men from the initial US prospective validation study, a race coefficient of 0.6 on the log-odds scale was prespecified. We calculated discrimination, calibration, and clinical utility of the 4Kscore with and without this coefficient for Black race in our primary analysis cohort of 205 Black men undergoing biopsy for PCa in a Veterans Affairs (VA) institution. We performed a sensitivity analysis using a combined cohort from the US prospective validation and the VA studies. RESULTS: The mean probability of high-grade PCa from the 4Kscore in the primary cohort increased from 25% to 37% with race coefficient addition. Incorporating the race coefficient improved 4Kscore's calibration in Black men, with consequent improvements in clinical utility based on decision curve analysis. Model discrimination was maintained (AUC 0.825 vs 0.828, P = .14) in the combined cohort of Black and non-Black men from the US prospective and VA studies and the calibration remained largely unchanged. CONCLUSIONS: Incorporating a prespecified coefficient for Black race improved calibration and clinical utility of the 4Kscore among Black men and should be added to the 4Kscore.

Refining parotid acinic cell carcinoma treatment: Balancing risk factors and extent of resection.

OBJECTIVES: Acinic cell carcinoma (ACC) most frequently arises in the parotid gland. Treatment consists of surgical resection and sometimes adjuvant therapy. ACC is most often a low-grade malignancy with good prognosis. Higher-grade tumors are often treated aggressively with total parotidectomy, neck dissection, and adjuvant therapy; however, the effect of parotid gland resection extent on oncologic outcomes has not been studied. Herein, we examine predictors of oncologic outcomes, including the effect of extent of resection. METHODS: Patients with diagnosis of parotid ACC treated at our institution were included in this retrospective study. Patient factors were examined, and patients were grouped by extent of resection and tumor grade. RESULTS: 58 patients, including 32 low-grade, 7 intermediate-grade, and 14 high-grade were included. Patients with low-grade tumors were more likely to undergo lesser extent of parotidectomy and less likely to undergo neck dissection. Two patients with low grade tumors developed recurrence, one local and one regional. Recurrence rate did not differ with resection extent in low-grade tumors. High tumor grade was found to be associated with disease progression. There was no association with adjuvant treatment and outcomes. Across all tumor grades advanced AJCC stage was found to be associated with disease progression. CONCLUSIONS: In ACC patients with low-grade tumors and lower disease stage who undergo lesser extent of surgical resection oncologic outcomes were favorable. Patients with high-grade tumors carry a high risk of recurrence, despite aggressive treatment. AJCC stage and histopathologic grade may predict outcomes and guide treatment.

A horizontally gene transferred copper resistance locus confers hyper-resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages.

Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) USA300, confers copper hyper-resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in emerging pathogenic isolates. Our data show that CopX, a putative P1B-3 -ATPase efflux transporter, and CopL, a novel lipoprotein, confer copper hyper-resistance compared to typical S. aureus strains. The copXL genes form an operon that is tightly repressed in low copper environments by the copper regulator CsoR. Significantly, CopX and CopL are important for S. aureus USA300 intracellular survival within macrophages. Therefore, the emergence of new S. aureus clones with the copXL locus has significant implications for public health because these genes confer increased resistance to antibacterial copper toxicity, enhancing bacterial fitness by altering S. aureus interaction with innate immunity.

Decarbamoylation of acetylcholinesterases is markedly slowed as carbamoyl groups increase in size.

Carbamates are esters of substituted carbamic acids that react with acetylcholinesterase (AChE) by initially transferring the carbamoyl group to a serine residue in the enzyme active site accompanied by loss of the carbamate leaving group followed by hydrolysis of the carbamoyl enzyme. This hydrolysis, or decarbamoylation, is relatively slow, and half-lives of carbamoylated AChEs range from 4 min to more than 30 days. Therefore, carbamates are effective AChE inhibitors that have been developed as insecticides and as therapeutic agents. We show here, in contrast to a previous report, that decarbamoylation rate constants are independent of the leaving group for a series of carbamates with the same carbamoyl group. When the alkyl substituents on the carbamoyl group increased in size from N-monomethyl- to N,N-dimethyl-, N-ethyl-N-methyl-, or N,N-diethyl-, the decarbamoylation rate constants decreased by 4-, 70-, and 800-fold, respectively. We suggest that this relationship arises as a result of active site distortion, particularly in the acyl pocket of the active site. Furthermore, solvent deuterium oxide isotope effects for decarbamoylation decreased from 2.8 for N-monomethylcarbamoyl AChE to 1.1 for N,N-diethylcarbamoyl AChE, indicating a shift in the rate-limiting step from general acid-base catalysis to a likely conformational change in the distorted active site.

Community pharmacist surveillance of hypertension in pregnancy: Are we ready for prime time?

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with serious maternal and perinatal complications. For nonsevere hypertension, there is a lack of consensus regarding treatment during pregnancy and while breastfeeding. Further, there is considerable variability in guidelines for antihypertensive drug choices. As part of a Drug Safety and Effectiveness Network (DSEN)-funded project, we piloted a novel surveillance strategy in which community pharmacists recruited pregnant and breastfeeding women to monitor their blood pressure and medication use and to provide education on HDP. METHODS: Participating pharmacists were required to complete a certified training program, identify and recruit patients who were pregnant or breastfeeding, obtain informed consent, administer a patient questionnaire and complete an initial case report form for enrolled patients. Study outcomes included the feasibility of community pharmacists to enroll patients and carry out study-related documentation and follow-up. The criteria for success in this pilot study included the ability of pharmacists to recruit 10 participants per pharmacy. RESULTS: 178 community pharmacies across British Columbia agreed to participate in this feasibility study, of which 63 pharmacists completed the study training. Of these, only 21 pharmacists recruited at least 1 patient and 1 pharmacist met the success criteria. Overall, 51 patients were enrolled, 2 withdrew from the study and 7 patients were diagnosed with HDP. Antihypertensive medications used by patients included methyldopa and labetalol. CONCLUSIONS: While postmarketing surveillance is an important tool for the assessment of drug safety in the pregnant and breastfeeding patient population, the feasibility of community pharmacists taking on this role was not successfully demonstrated.

Long-term impact of commonly performed operations in pediatric urology on reproductive and sexual health.

Introduction: Sexual dysfunction is highly prevalent among men of reproductive age. Clinical practice guidelines have been established to assist providers in identification and education of patients who are at increased risk for infertility and sexual dysfunction with certain congenital and acquired urogenital disorders. The authors sought to review the reproductive and sexual health implications of treating common childhood urological conditions with commonly performed surgical procedures. Methods: To ensure the inclusion of influential and highly regarded research, we prioritized citations from the most-frequently cited articles on our respective review topics. Our inclusion criteria considered studies with substantial sample sizes and rigorously designed methodologies. Several topics were reviewed, including penile chordee, hypospadias, posterior urethral valves, varicoceles, undescended testicles, and testicular torsion. Results: For chordee, surgical plication or corporal grafting may be employed. Erectile function remains unaltered post-surgery, while penile length may decrease after repair, which may be avoided using dermal grafts. Hypospadias repair hinges on severity and availability of the urethral plate. Those who underwent hypospadias repair report decreased penile length, but sexual satisfaction, libido, and semen quality are comparable to controls. Posterior urethral valves are usually treated with valve ablation. While valve ablation and bladder neck incision have not been found to affect ejaculatory function, high degree of concurrent renal dysfunction related to nephrogenic and bladder dysfunction may impact semen parameters and erectile function. Regarding varicocele, earlier management has been associated with better long-term fertility outcomes, and surgical intervention is advisable if there is observable testicular atrophy. Earlier repair of undescended testicle with orchiopexy has been found to improve fertility rates as well as decrease malignancy rates. Unilateral orchiectomy for testicular torsion without the ability for salvage has been shown to have decreased semen parameters but unaffected fertility rates. Conclusion: Infertility and sexual dysfunction are multivariable entities, with etiologies both congenital and acquired. At the same time, many common pediatric urology surgeries are performed to correct anatomic pathology that may lead to reproductive dysfunction in adulthood. This review highlights the need for diagnosis and management of pediatric urologic conditions as these conditions may impact long-term sexual function post-operatively.

Long-term impact of commonly performed operations in pediatric urology on sexual health Many men of reproductive age face sexual health challenges, prompting the creation of guidelines for identifying and addressing issues related to urogenital disorders. This study explores the impacts of common surgical procedures on reproductive and sexual health in children with urological conditions. By reviewing extensive literature, the study focuses on the long-term effects of pediatric urologic surgeries, emphasizing influential and frequently cited research for a comprehensive understanding. For conditions like chordee, surgical options such as plication or grafting may be considered. While erectile function typically remains unchanged, there might be a decrease in penile length post-surgery, which can be addressed with specific techniques. Hypospadias repair varies based on severity, with those undergoing the procedure having shorter penises. However, their sexual satisfaction, libido, and semen quality are comparable to others. Treatment of posterior urethral valves (PUV) often involves valve ablation, however some studies have shown altered semen parameters following ablation. Managing varicocele early on leads to better outcomes, and surgery is recommended if testicular atrophy is observed. Orchiopexy and orchiectomy are procedures for undescended testis (UDT) and testicular torsion in children. Pediatric urologic diseases and their surgical interventions can significantly affect sexual function and fertility in adulthood due to their multifactorial nature. While some procedures aim to preserve or enhance sexual potential such as proper urethral development, others may inadvertently impact sexual health negatively, such as necrotic testes removal. This underscores the importance of thorough diagnosis and management of pediatric urologic conditions to safeguard long-term sexual function post-surgery.

Increasing recognition of happiness in ambiguous facial expressions reduces anger and aggressive behavior.

The ability to identify emotion in other people is critical to social functioning. In a series of experiments, we explored the relationship between recognition of emotion in ambiguous facial expressions and aggressive thoughts and behavior, both in healthy adults and in adolescent youth at high risk of criminal offending and delinquency. We show that it is possible to experimentally modify biases in emotion recognition to encourage the perception of happiness over anger in ambiguous expressions. This change in perception results in a decrease in self-reported anger and aggression in healthy adults and high-risk youth, respectively, and also in independently rated aggressive behavior in high-risk youth. We obtained similar effects on mood using two different techniques to modify biases in emotion perception (feedback-based training and visual adaptation). These studies provide strong evidence that emotion processing plays a causal role in anger and the maintenance of aggressive behavior.

A case report on the prolonged viability of postmortem human testicular sperm.

Objective: To report a case of postmortem sperm retrieval with prolonged viability and motility. Design: Case report. Setting: Hospital and Medical Examiner Department. Patients: A 44-year-old African American male patient with a history of recreational marijuana use and occasional alcohol consumption who died from a cardiac arrest because of drug overdose. Interventions: Multiple testicular biopsies and sperm analyses. Main Outcome Measures: Sperm viability and motility of testicular biopsies at serial time intervals. Results: Sperm obtained from the testis in the morgue remained viable and motile even at 106 hours (>4 days) postmortem. Conclusions: Our study found that sperm obtained from the testis remained viable and motile even after being thawed after cryopreservation, even when obtained up to 100 hours postmortem. This may have implications on the timeframe that postmortem sperm retrieval can be performed successfully several days after death.

Stem-Cell, Shockwave, and Platelet Rich Plasma Therapy for the Treatment of Erectile Dysfunction and Peyronie's Disease: A Survey of Clinics Across the USA.

OBJECTIVE: To identify clinics offering off-label therapies for erectile dysfunction (ED) and Peyronie's disease (Pyd) including stem cell, platelet-rich plasma (PRP), and shockwave therapy and to determine the transparency they provided to patients inquiring about these treatment modalities. METHODS: Clinics were identified in different regions in the US using a systematic search on online website directories and were approached by asking a series of standardized questions regarding the cost of treatment, duration of therapy, the medical staff involved, and patient outcome data. A total of 26 clinics were surveyed for stem cell therapy, 26 for PRP treatment, and 27 for shockwave therapy. RESULTS: Of the 79 clinics contacted, 93.7% provided some answers to the questions we asked, with a majority offering treatments for both ED and Pyd. The cost of treatment varied widely between clinics. The average cost per stem cell therapy injection was $5291, PRP per injection was $1336, and shockwave therapy per session was $413. A physician was involved in 67% of treatments, and only 6 of 79 clinics reported that a urologist was involved. Over 75% of the clinics reported patient satisfaction following treatment. Durability of benefits to patients ranged from months to years according to the clinics' reports. CONCLUSION: Our data not only demonstrate the widespread use of off-label therapies for ED and PyD across the United States but also the lack of scientific data to support the claims made to patients. This study highlights the need for more oversight and standardization in novel regenerative therapies for ED and PyD.

Fertility outcomes in men with prior history of anabolic steroid use.

OBJECTIVE: To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized treatment regimen for spermatogenesis recovery. DESIGN AND SUBJECTS: A retrospective analysis of a cohort of men with a prior history of anabolic steroid use and infertility complaints (between 2018 and 2022) was conducted. EXPOSURE: The standardized treatment approach involved discontinuing testosterone replacement therapy and administering a combination regimen of clomiphene citrate and human chorionic gonadotropin for a minimum of 3 to 6 months. MAIN OUTCOME MEASURES: The main outcome measures included changes in sperm parameters, predominantly sperm concentration, and subsequent pregnancy outcomes. RESULTS: A total of 45 men (median age 37 years, IQR 32-45) met the inclusion criteria for this analysis. Median duration of prior T use was 4 years (IQR 1.3-10), with the 2 most common modalities consisting of injection therapy (43.5%) and oral therapy (34.8%). The median initial sperm concentration was 0 million/cc (IQR 0-1.15), and 23 (51.1%) men initially presented with azoospermia. The median duration of combination human chorionic gonadotropin/clomid therapy was 5 months (IQR 3-12). In initially azoospermic men (N: 23), 5 were lost to follow-up, 6 (33.3%) progressed to severe oligospermia (<5 million/cc), 6 (33.3%) to oligospermia (<15 million/cc), 1 (5.6%) to normozoospermia (>15 million/cc), and 5 (27.8%) remained azoospermic after medical treatment for 6 months. Among the 24 couples who responded to the follow-up call, a total of 9 (37.5%) achieved a successful subsequent pregnancy. Of these, 33.3% (3 couples) used assisted reproductive technology, whereas 66.7% (6 couples) conceived naturally. On logistic regression analysis, no significant predictors for improved sperm parameters or successful pregnancy were identified. CONCLUSION: Despite appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with more than half showing limited improvement in semen parameters after 6 months of treatment. Only a fraction of men achieves normozoospermia after treatment. Further research is needed to explore predictors for improved sperm parameters and successful pregnancy outcomes in men with a history of anabolic steroid use.

Biopsychosocial approach to male chronic pelvic pain syndrome: recent treatments and trials.

INTRODUCTION: Chronic pelvic pain syndrome (CPPS) is a common urologic condition that can cause significant disability in affected individuals. Physiologic explanations of chronic pain are often incomplete; appropriate management of CPPS includes recognition of biological, psychological, and social elements, known as the biopsychosocial model. OBJECTIVE: The aim of this narrative review is to investigate treatments for men with CPPS, with a special focus on those utilizing the biopsychosocial model of care. METHODS: A comprehensive literature search was conducted on the electronic databases PubMed, Embase, and Cochrane Library, using relevant Medical Subject Heading terms and keywords related to CPPS treatments. The search was limited to studies published in English from inception to January 2023. Additionally, reference lists of selected studies were manually reviewed to find studies not identified by the initial search. Studies were included if they investigated pharmacologic or nonpharmacologic treatments for men with CPPS. RESULTS: A total of 30 studies met the inclusion criteria. Antibiotics, α-blockers, nonsteroidal anti-inflammatory drugs, gabapentinoids, antidepressants, and phosphodiesterase type 5 inhibitors were among the pharmacologic agents included in trials attempting to reduce symptoms of male CPPS. Studies that focused on treating CPPS without medication included interventions such as shockwave therapy, acupuncture, physical therapy, botulinum toxin, cryotherapy, electrotherapy, exercise, and cognitive behavioral therapy. CONCLUSION: α-Blockers and nonsteroidal anti-inflammatory drugs have shown promising results in treating CPPS in men, while the effectiveness of antibiotics remains controversial. Antidepressants and phosphodiesterase type 5 inhibitors may also be useful in decreasing symptoms in patients with CPPS. Treatments such as pelvic floor muscle therapy, acupuncture, shockwave therapy, and cognitive behavioral therapy must be considered effective complements to medical management in men with CPPS. While these interventions demonstrate benefits as monotherapies, the individualization and combination of treatment modalities are likely to result in reduced pain and improved quality of life.

Significant Publications on Infectious Diseases Pharmacotherapy in 2022.

Purpose: To provide summarization of the most significant infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature in 2022. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated notable articles providing significant contributions to ID pharmacotherapy in 2022. Article nominations included those pertaining to general ID, as well as those including coronavirus disease 2019 (COVID-19), and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy. A total of 71 articles were nominated by HIDN. Members: 68 articles pertaining to general ID pharmacotherapy and 3 articles focusing on HIV/AIDS. To aid selection of the most these most notable articles of 2022, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP). Of the 153 SIDP members who participated in the survey, there were 128 recorded votes for the top 10 general ID pharmacotherapy articles and 30 votes recorded for the top HIV/AIDS article. The most notable publications are summarized. Conclusion: Post pandemic significant advances in antimicrobial stewardship and infectious disease states continues to occur in a world recently focused on the coronavirus disease 2019 (COVID-19) global pandemic. Continuous growth in publication of ID-related articles over the past year lends towards the aims of this review to aid clinicians in remaining current on key practice-changing ID pharmacotherapy publications from 2022.

Exploring representation of underrepresented minority men in a restorative therapy clinical trial for erectile dysfunction: addressing barriers and promoting inclusion.

This retrospective descriptive analysis explores underrepresented minority men in our clinical trial for restorative therapy for erectile dysfunction and to identify strategies to promote diversity and inclusion in the study population. Demographic data were collected from all participants and the prevalence in our population was compared to the source population. The proportion of individuals taking part in our clinical trial was compared to the overall disease population using the participation to prevalence ratio. Among the 61 participants enrolled in the Platelet-Rich Plasma for Erectile Dysfunction trial, 72.1% were Hispanic compared to 39.9% in the national source population. There were 27.9% non-Hispanic participants, and 41.2% non-Hispanic men in the local South Florida population. The racial composition of our study shows 80.3% of PRP participants identify as White, 16.4% as Black, and 3.4% as Asian. In the national source population, 61.8% of patients were White, 27.5% are black, and 1.5% are Asian. Through the implementation of strategies such as having Hispanic team members on the clinical trial staff and providing education and outreach materials both in Spanish and English, we were able to overcome barriers to participation in Hispanic men and potentially improve health outcomes for underrepresented minority men with erectile dysfunction.

Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study.

Introduction Infertility and hypogonadism in males can greatly affect their reproductive health and overall well-being. Since exogenous testosterone administration for hypogonadism management may disrupt the normal hormonal cascade necessary for spermatogenesis, clomiphene citrate (CC) and enclomiphene citrate (EC) are medications often used to manage hypogonadism and male infertility. This study aims to directly compare the effects of CC and EC on serum testosterone levels and semen parameters in men to determine which medication may have an advantage in managing these conditions. Materials and methods We retrospectively analyzed ≥18-year-old men presenting with primary infertility, abnormal semen parameters, or hypogonadism who received CC or EC monotherapy for at least three months between January 2021 and December 2022. We compared baseline and follow-up hormone levels, semen parameters, and demographics. Variables were compared using paired and unpaired t-tests. Significance was assessed at p<0.05. Results A total of 46 men received EC and 32 men received CC. The median age was 42 (IQR: 34-47.75) years in men who received EC and 41 (IQR: 36-44) years in men who received CC (p=0.450). The two treatment groups exhibited a significant increase in serum total testosterone, while only EC had a statistically significant increase in FSH and LH. Semen volume and concentration did not significantly change with either treatment. Sperm motility increased in both groups, but total motile sperm count (TMSC) only significantly increased in men who received EC.  Conclusions Our study found that EC and CC are effective treatments in increasing total testosterone without negatively affecting spermatogenesis. EC demonstrated to be more effective in raising gonadotropin levels and TMSC.

A multi-institutional study of 1,111 men with 4K score, multiparametric magnetic resonance imaging, and prostate biopsy.

OBJECTIVE: Prostate magnetic resonance imaging (MRI) and biomarkers are often used in conjunction to enhance the selection process for prostate biopsy. However, the optimal sequence of ordering these tests has not been established. A comprehensive evaluation was conducted on a large multi-institutional cohort of patients who underwent MRI, 4K score, and biopsy of the prostate to examine the impact of utilizing both tests vs. either test alone and to determine if the order in which these tests are administered affects the ability to detect clinically significant prostate cancer (csCaP). METHODS AND MATERIALS: We evaluated men from 8 different institutions who were referred for prostate cancer evaluation and underwent MRI, 4K score test, and prostate biopsy. The primary outcome was the presence of csCaP, defined as grade group 2 or higher cancer on a biopsy of the prostate. We used logistic regression, calibration plots, and decision curve analysis to evaluate using a 4K score or MRI alone vs. both tests together for detecting csCaP. In addition, we evaluated several strategies using one or both tests for selecting men for biopsy and compared them based on the proportion of biopsies avoided and the csCaP's missed. RESULTS: Among the 1,111 men who formed the final cohort, 553 (49.8%) had prostate cancer, and 353 (31.8%) had csCaP. We found that using MRI and 4K score together had better discrimination, calibration, and a higher clinical utility on decision curve analysis compared to using either test individually. Using both tests together resulted in fewer biopsies avoided and missed cancers compared to using either test alone. Strategies that sequence MRI and 4K score tests resulted in the largest biopsy reduction, with no appreciable difference between starting with an MRI vs. a biomarker. CONCLUSIONS: We found that using both an MRI and 4K score together was superior to using either test alone but found no appreciable difference between starting with an MRI vs. starting with a 4K score. Prospective studies are needed to identify the best strategy to sequence MRI and biomarkers in the evaluation of csCaP.

Optimum threshold of the 4Kscore for biopsy in men with negative or indeterminate multiparametric magnetic resonance imaging.

Objective: The study aims to identify the optimal 4Kscore thresholds to determine the need for a prostate biopsy when multiparametric magnetic resonance imaging (MRI) (mpMRI) is negative or indeterminate. Materials and methods: We analysed retrospective data from men in eight different institutions who underwent an mpMRI, 4Kscore and prostate biopsy for evaluation of prostate cancer. We selected men with a negative (PIRADS ≤2) or indeterminate (PIRADS 3) mpMRI. 4Kscore values were categorized into ranges of 1-7, 8-19, 20-32 and greater than 32. We evaluated the proportion of men with grade group 2 or higher (GG2+) cancer in groups defined by PIRADS and 4Kscore. We also evaluated the number of biopsies avoided and GG2+ cancer missed in each group reported depend on 4Kscore cutoff points. Results: Among 1111 men who had an mpMRI, 4Kscore and biopsy, 625 of them had PIRADS ≤3 on mpMRI: 374 negative (PIRADS ≤2) and 251 indeterminate (PIRADS 3). In men with a negative mpMRI, we found a 4Kscore cut-point of 33 resulted in an increased risk of GG2+ cancer on biopsy. In patients with an equivocal lesion on mpMRI, men with a 4Kscore cutoff ≥8 had a greater risk of GG2+ cancer on biopsy. Decision curve analysis supported the proposed cut-points in each mpMRI group. Conclusions: In men with negative and indeterminate mpMRI, we found the best 4Kscore threshold to determine the need for biopsy to be 33 and 8 respectively. Future prospective studies in independent populations are needed to confirm these findings.

Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Failure to recognize symptoms of non-human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(-)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(-)OPSCC. METHODS: Retrospective review at a tertiary care center. Patients with HPV(-)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care. RESULTS: Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32-127 days), with a median latency of 30 days (IQR = 12-61 days) from symptom onset to first presentation and 19.5 days (IQR = 4-46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis. CONCLUSIONS: Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(-)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(-)OPSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1394-1401, 2023.

Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies.

OBJECTIVE: To determine the magnitude of the risk of incident cardiovascular disease (CVD; fatal and non-fatal), including acute myocardial infarction (MI), cerebrovascular accidents (CVA) and congestive heart failure (CHF), in patients with rheumatoid arthritis (RA) compared to the general population through a meta-analysis of controlled observational studies. METHODS: The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic. RESULTS: Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)). CONCLUSIONS: Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis (ANMDARE) in a Patient With Hashimoto's Thyroiditis.

Although encephalitis is more commonly caused by various infections, other etiologies that may rarely cause encephalitis must garner the attention of medical practitioners. In the realm of immune-mediated etiologies, anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is the most common. It usually presents in a typical fashion with psychiatric symptoms followed by abnormal movements such as orofacial-lingual dyskinesia, tremor, dystonia, bradykinesia, ballism, or choreoathetosis occurring at or within the first month of onset, often affecting women and having a high correlation with ovarian teratomas. Our case report describes a 59-year-old Hispanic male with Hashimoto thyroiditis who presented with rapid cognitive decline. The diagnosis was confirmed with positive detection of NMDA receptor antibodies in the patient's cerebrospinal fluid following a lumbar puncture. The patient was treated with the first-line therapy of intravenous (IV) immunoglobulins and corticosteroids with temporary relief of symptoms. Due to the rare occurrence and possible atypical presentation of ANMDARE, this case illustrates the importance of maintaining a high index of clinical suspicion when diagnosing a patient with an unknown cause of cognitive dysfunction, especially when considering various differentials based on the patient's history.